Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

The clinical results of lung transplantation (LTx) are still less favorable than other solid organ transplants in both the early and long term. The fragility of the lungs limits the procurement rate and can favor the occurrence of ischemia-reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) with...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-01, Vol.22 (2), p.510
Main Authors: Miceli, Vitale, Bertani, Alessandro, Chinnici, Cinzia Maria, Bulati, Matteo, Pampalone, Mariangela, Amico, Giandomenico, Carcione, Claudia, Schmelzer, Eva, Gerlach, Jörg C, Conaldi, Pier Giulio
Format: Article
Language:English
Subjects:
Alveoli
Amnion
amnion-derived mesenchymal stem cells
Apoptosis
Blood & organ donations
Catheters
Cold
conditioned medium
Cytokines
Epithelial cells
ex vivo lung perfusion
Fragility
Growth factors
Inflammation
Ischemia
lung ischemia-reperfusion injury
Lungs
Mesenchyme
Paracrine signalling
Perfusion
Placenta
Reperfusion
Spheroids
Stem cells
Transplantation
Transplants
Transplants & implants
Two dimensional models
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Summary:The clinical results of lung transplantation (LTx) are still less favorable than other solid organ transplants in both the early and long term. The fragility of the lungs limits the procurement rate and can favor the occurrence of ischemia-reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) with Steen Solution (SS) aims to address problems, and the implementation of EVLP to alleviate the activation of IRI-mediated processes has been achieved using mesenchymal stromal/stem cell (MSC)-based treatments. In this study, we investigated the paracrine effects of human amnion-derived MSCs (hAMSCs) in an in vitro model of lung IRI that includes cold ischemia and normothermic EVLP. We found that SS enriched by a hAMSC-conditioned medium (hAMSC-CM) preserved the viability and delayed the apoptosis of alveolar epithelial cells (A549) through the downregulation of inflammatory factors and the upregulation of antiapoptotic factors. These effects were more evident using the CM of 3D hAMSC cultures, which contained an increased amount of immunosuppressive and growth factors compared to both 2D cultures and encapsulated-hAMSCs. To conclude, we demonstrated an in vitro model of lung IRI and provided evidence that a hAMSC-CM attenuated IRI effects by improving the efficacy of EVLP, leading to strategies for a potential implementation of this technique.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22020510